tbuckley/cabot-search huggingface dataset:
Measurement of Serum N-Glycans in the Assessment of Early Vascular Aging (Arterial Stiffness) in Adults With Type 1 Diabetes
Authors: Gemma Llauradó, Núria Amigó, Rocío Fuertes-Martín, Ana Romero, Albert Cano, Lara Albert, Olga Giménez-Palop, Eugenio Berlanga, Sonia Fernández-Veledo, Xavier Correig, Joan Vendrell, José-Miguel González-Clemente
Journal: Diabetes Care (2022)

OBJECTIVE Vascular aging (arterial stiffness [AS]) is an inflammation-linked process that predicts macro- and microvascular complications in adults with type 1 diabetes (T1D). We evaluated the utility of measuring the inflammation-linked N-glycans GlycA and GlycB to assess vascular aging in adults with T1D. RESEARCH DESIGN AND METHODS Eighty-four adults with T1D (&amp;gt;10-year duration without cardiovascular events) and 68 healthy control subjects were evaluated for clinical characteristics (including microvascular complications in patients with T1D), aortic pulse wave velocity (aPWV) (surrogate measure of AS), and serum GlycA and GlycB (peak area [concentration] and height/width [H/W] ratio) using 1H-nuclear magnetic resonance spectroscopy. RESULTS Patients with T1D had higher median (interquartile range) values than healthy control subjects for (P &amp;lt; 0.001 for all comparisons) aPWV 7.9 (6.9–9.1) vs. 6.1 (5.5–6.7) m/s, GlycA 850.4 (781.3–916.1) vs. 652.4 (581.5–727.1) μmoL; GlycB 386.1 (353.2–426.3) vs. 310.0 (280.5–331.9) μmol/L), H/W ratio of GlycA 16.5 (14.9–18.1) vs. 15.0 (13.7–16.7), and H/W ratio of GlycB 5.0 (4.6–5.5) vs. 4.0 (3.4–4.3). Moreover, aPWV correlated (P &amp;lt; 0.001 for all correlations) with GlycA (r = 0.550) and GlycB (r = 0.423) concentrations and with H/W ratios of GlycA (r = 0.453) and GlycB (r = 0.510). Adjusting for potential confounders, GlycA concentration (β = 0.212, P &amp;lt; 0.001) and the H/W ratios of GlycA (β = 0.150, P = 0.009) and GlycB (β = 0.155, P = 0.011) remained independently associated with aPWV. C-statistics for detecting individuals with aPWV &amp;gt;10 m/s were 0.866 (95% CI 0.794–0.937) for GlycA levels and 0.862 (0.780–0.943) for H/W ratio of GlycB. CONCLUSIONS Measurement of serum GlycA and GlycB may have utility in assessing vascular aging in adults with T1D of &amp;gt;10-year duration and no previous cardiovascular events.
Matrix Metalloproteinase-2 Contributes to Cancer Cell Migration on Collagen
Authors: Xiaoping Xu, Yao Wang, Zhihua Chen, Mark D. Sternlicht, Manuel Hidalgo, Bjorn Steffensen
Journal: Cancer Research (2005)

Abstract Matrix metalloproteinases (MMP) are central to tissue penetration by cancer cells, as tumors expand and form metastases, but the mechanism by which MMP-2 contributes to cancer cell migration is not well understood. In the present experiments, both a broad-spectrum MMP inhibitor and the isolated collagen binding domain (CBD) from MMP-2 inhibited cell migration on native type I collagen. These results verified the involvement of MMPs in general and showed that MMP-2, specifically, contributes to cell migration by a mechanism involving MMP-2 interaction with collagen. To exclude potential overlapping effects of MMP-9, additional experiments showed that MMP-2 also contributed to migration of MMP-9−/− cells. To investigate whether the homologous CBD from human fibronectin also inhibited cell migration, we first showed that fragmentation of fibronectin is a feature of breast cancer tumors and that several fragments contained the CBD. However, the recombinant fibronectin domain did not alter cell migration on collagen. This lack of effect on cell migration was explored in competitive protein-protein binding assays, which showed that the affinity of MMP-2 for collagen exceeds that of fibronectin. Furthermore, whereas the isolated MMP-2 CBD inhibited the gelatinolytic activities of MMP-2 and tumor extracts, such an inhibition was not characteristic of the corresponding fibronectin domain. Together, our results provide evidence that MMP-2 is an important determinant of cancer cell behavior but is not inhibited by the collagen binding segment of fibronectin.
The University of Texas Medical Branch at Galveston
Authors: Chester R. Burns
Journal: JAMA (1991)

THOSE entering the east end of Galveston Island on the free ferry from Bolivar Peninsula soon encounter a large white water tower inscribed "Galveston Island—Home of UTMB." A quick glance reveals a cluster of tall buildings, some of the 70 structures that make up the campus of the University of Texas Medical Branch (UTMB). If arriving at night, they see a huge white-and-green—lit sign adorning one building: UTMB Galveston/John Sealy Hospital. How, some surely wonder, did this large health sciences center get established on this rather unlikely spot, a sandy barrier island in the northern Gulf of Mexico? <h3>QUEEN CITY OF THE GULF</h3> After Texas became a state in 1845, its population grew from around 200 000 in 1850 to more than 600 000 by 1860.<sup>1</sup>A hub of migrant and commercial bustle with more than 20 000 citizens, Galveston became the state's largest, wealthiest city by the mid-1870s.<sup>2</sup>
Recent Changes in Attack and Survival Rates of Acute Myocardial Infarction (1975 Through 1981)
Authors: Robert J. Goldberg
Journal: JAMA (1986)

A communitywide study was conducted in all 16 acute general hospitals in the metropolitan Worcester, Mass, area during the calendar years 1975, 1978, and 1981 to examine time trends in the attack and case-fatality rates of patients hospitalized with validated acute myocardial infarction as well as of the occurrence of out-of-hospital coronary heart disease (CHD) deaths. Between 1975 and 1981, there was an increase in the age-adjusted attack rates of initial events of acute myocardial infarction (1975, 254/100,000; 1981, 280/100,000) as well as recurrent events (1975, 133/100,000; 1981, 156/100,000). These overall increases were due to an increase among those 65 years of age and older, with no significant changes observed in those less than 65 years old. The age-adjusted in-hospital case-fatality rates declined from 22.1% in 1975 to 20.3% in 1978 and 17.4% in 1981. In examining long-term prognosis, no significant differences were seen over an eight-year follow-up period between patients discharged in 1975, 1978, and 1981. The age-adjusted mortality rates of out-of-hospital CHD deaths significantly declined between 1975 (229/100,000) and 1981 (147/100,000). The results of this population-based survey suggest that recently observed declines in the mortality rates of CHD may reflect decreases in out-of-hospital coronary deaths and improving trends in the in-hospital survival of patients with acute myocardial infarction. (<i>JAMA</i>1986;255:2774-2779)
A translation re-initiation variant in KLHL24 also causes epidermolysis bullosa simplex and dilated cardiomyopathy via intermediate filament degradation
Authors: Mathilde C.S.C. Vermeer, Mohammad Al-Shinnag, Herman H.W. Silljé, Antonio Esquivel Gaytan, Dedee F. Murrell, Julie McGaughran, Wei Melbourne, Timothy Cowan, Peter C. van den Akker, Karin Y. van Spaendonck-Zwarts, Peter van der Meer, Maria C. Bolling
Journal: British Journal of Dermatology (2022)

This study shows that gain-of-function variants in KLHL24 causing EBS and DCM, do not only originate in the start-codon and suggest that any nonsense-inducing variant affecting nucleotides c.4_84 will likely cause the same effect on protein level and a similar potential lethal phenotype.
The 1940 Year Book of Industrial and Orthopedic Surgery
Journal: JAMA (1941)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Triple MAPK inhibition salvaged a relapsed post-BCMA CAR-T cell therapy multiple myeloma patient with a BRAF V600E subclonal mutation
Authors: Muhammad Elnaggar, Sarita Agte, Paula Restrepo, Meghana Ram, David Melnekoff, Christos Adamopoulos, Mark M. Stevens, Katerina Kappes, Violetta Leshchenko, Daniel Verina, Sundar Jagannath, Poulikos I. Poulikakos, Samir Parekh, Alessandro Laganà
Journal: Journal of Hematology & Oncology (2022)

Abstract Background Multiple Myeloma (MM) is a progressive plasma cell neoplasm characterized by heterogeneous clonal expansion. Despite promising response rates achieved with anti-BCMA CAR-T cell therapy, patients may still relapse and there are currently no clear therapeutic options in post-CAR-T settings. In this report, we present a case of a post-BCMA CAR-T relapsed/refractory (RR) MM patient with skin extramedullary disease (EMD) in which a novel MAPK inhibition combinatorial strategy was implemented based on next-generation sequencing and in vitro experiments. Case presentation A 61-year-old male with penta-refractory MM penta- (IgA lambda), ISS stage 3 with hyperdiploidy, gain of 1q21 and del13 was treated with anti-BCMA CAR-T cell therapy, achieving a best response of VGPR. He progressed after 6 months and was salvaged for a short period with autologous stem cell transplantation. Eventually, he progressed with extramedullary disease manifested as subcutaneous nodules. Based on whole-exome sequencing, we identified a BRAF (V600E) dominant subclone in both bone marrow and cutaneous plasmacytoma. Following in vitro experiments, and according to our previous studies, we implemented a triple MAPK inhibition strategy under which the patient achieved a very good partial response for 110 days, which allowed to bridge him to subsequent clinical trials and eventually achieve a stringent complete response (sCR). Conclusion Here, we show the applicability, effectiveness, and tolerability the triple MAPK inhibition strategy in the context of post-BCMA CAR-T failure in specific subset of patients. The triple therapy could bridge our hospice bound RRMM patient with BRAF (V600E) to further therapeutic options where sCR was achieved. We will further evaluate triple MAPK inhibition in patients with BRAF V600E in a precision medicine clinical trial launching soon.
Topical treatments in the management of keloids and hypertrophic scars: a critically appraised topic
Authors: Sina J. Ghadiri, Ewa Kloczko, Carsten Flohr
Journal: British Journal of Dermatology (2022)

Keloids and hypertrophic scars remain a frustrating and common entity posing continued challenges. A case of an 8‐year‐old girl with a painful keloid scar on the right arm subsequent to a history of varicella zoster virus inspired us to review the available evidence on the best treatment modality, given her substantial needle phobia. There is a plethora of treatment options available in the pursuit of their notoriously difficult elimination; however, none is more accessible, cheap or patient centric than topical treatments.1 We searched the MEDLINE and Embase databases and the Clinical Trials Registry from inception to 7 January 2022. The findings are summarized in a PRISMA flow diagram (https://doi.org/10.6084/m9.figshare.19874242.v1). The studies exhibited a high degree of heterogeneity in designs and methods with notable variation in outcome measurement across studies, and therefore meta‐analysis was not performed. The Cochrane Risk of Bias tool (Figure 1) emphasizes further the impact of selection, performance and detection bias, alongside the prevalence of incomplete outcome data.
Management of Patients With Peripheral Artery Disease (Compilation of 2005 and 2011 ACCF/AHA Guideline Recommendations)
Authors: Jeffrey L. Anderson, Jonathan L. Halperin, Nancy M. Albert, Biykem Bozkurt, Ralph G. Brindis, Lesley H. Curtis, David DeMets, Robert A. Guyton, Judith S. Hochman, Richard J. Kovacs, E. Magnus Ohman, Susan J. Pressler, Frank W. Sellke, Win-Kuang Shen
Journal: Circulation (2013)
Tapinarof Cream 1%: First Approval
Authors: Susan J. Keam
Journal: Drugs (2022)

Tapinarof cream 1% (VTAMA®) is an aryl hydrocarbon receptor (AhR) agonist that is being developed by Dermavant Sciences Inc. (a subsidiary of Roivant Sciences Inc.) as a once-daily topical treatment for plaque psoriasis and atopic dermatitis. AhR is a ligand-dependent transcription factor that has a role in immune-mediated skin responses. In May 2022, tapinarof cream 1% was approved in the USA for the topical treatment of plaque psoriasis in adults. Tapinarof cream 1% is also being investigated for the treatment of atopic dermatitis. This article summarizes the milestones in the development of tapinarof cream 1% leading to this first approval for the topical treatment of plaque psoriasis.
Resistance Evolution against Host-directed Antiviral Agents: Buffalopox Virus Switches to Use p38-ϒ under Long-term Selective Pressure of an Inhibitor Targeting p38-α
Authors: Yogesh Chander, Ram Kumar, Assim Verma, Nitin Khandelwal, Himanshu Nagori, Namita Singh, Shalini Sharma, Yash Pal, Apurvasinh Puvar, Rameshchandra Pandit, Nitin Shukla, Priyank Chavada, Bhupendra N Tripathi, Sanjay Barua, Naveen Kumar
Journal: Molecular Biology and Evolution (2022)

Abstract Host-dependency factors have increasingly been targeted to minimize antiviral drug resistance. In this study, we have demonstrated that inhibition of p38 mitogen-activated protein kinase (a cellular protein) suppresses buffalopox virus (BPXV) protein synthesis by targeting p38-MNK1-eIF4E signaling pathway. In order to provide insights into the evolution of drug resistance, we selected resistant mutants by long-term sequential passages (P; n = 60) in the presence of p38 inhibitor (SB239063). The P60-SB239063 virus exhibited significant resistance to SB239063 as compared to the P60-Control virus. To provide mechanistic insights on the acquisition of resistance by BPXV-P60-SB239063, we generated p38-α and p38-ϒ (isoforms of p38) knockout Vero cells by CRISPR/Cas9-mediated genome editing. It was demonstrated that unlike the wild type (WT) virus which is dependent on p38-α isoform, the resistant virus (BPXV-P60-SB239063) switches over to use p38-ϒ so as to efficiently replicate in the target cells. This is a rare evidence wherein a virus was shown to bypass the dependency on a critical cellular factor under selective pressure of a drug.
Journal club
Authors: Sophie Masterson
Journal: Thorax (2022)

Purinergic signalling and sensitisation of P2X 3 receptors on the vagus nerve have been implicated in the mechanism of chronic cough.McGarvey et al assessed the efficacy and safety of gefapixant, a P2X 3 receptor antagonist for the treatment of chronic cough in two phase 3 trials: COUGH-1 and COUGH-2 (Lancet 2022;399:909).Both were multinational double-blind, placebo-controlled, parallel group studies comparing 15 mg and 45 mg dosing, 1:1:1 allocation.COUGH-1 ran over a 12-week study period (n=732) and COUGH-2 over 24 weeks (n=1317).Patients with a diagnosis of unexplained chronic cough or refractory chronic cough (despite optimal medical management of associated comorbidity) for over 1 year were included.Current smokers and patients with forced expiratory volume in one second (FEV 1 ):forced vital capacity ratio <0.6 or abnormal chest imaging were excluded.The primary endpoint was reduction in 24-hour cough frequency in treatment groups versus placebo.Secondary endpoints included clinically significant improvement in Leicester Cough Questionnaire score.Results were similar in both studies: at 12 weeks in COUGH-1, there was a 53% reduction in cough frequency in placebo group, 52% in 15 mg group and 62% reduction in 45 mg group.COUGH-2 reported 57%, 57% and 63% reductions, respectively.Adverse effects predominantly related to taste disturbance: 20% of COUGH-2 participants in the 45 mg group discontinued the study due to adverse events (vs rates of 4.8% in placebo and 7.7% in 15 mg groups).Although 45 mg two times per day of gefapixant achieved a significant relative reduction in cough frequency versus placebo, this was overshadowed by the high rates of adverse effects and significant placebo effect.
Derivation of prognostic contextual histopathological features from whole-slide images of tumours via graph deep learning
Authors: Yongju Lee, Jeong Hwan Park, Sohee Oh, Kyoungseob Shin, Jiyu Sun, Minsun Jung, Cheol Lee, Hyojin Kim, Jin-Haeng Chung, Kyung Chul Moon, Sunghoon Kwon
Journal: Nature Biomedical Engineering (2022)
Outcomes of renal transplantation in patients with AL amyloidosis: an international collaboration through The International Kidney and Monoclonal Gammopathy Research Group
Authors: Andrea Havasi, Cihan Heybeli, Nelson Leung, Avital Angel-Korman, Vaishali Sanchorawala, Oliver Cohen, Ashutosh Wechalekar, Frank Bridoux, Insara Jaffer, Victoria Gutgarts, Hani Hassoun, Maya Levinson, Cara Rosenbaum, Paolo Milani, Giovanni Palladini, Giampaolo Merlini, Ute Hegenbart, Stefan Schönland, Kaya Veelken, Alexander Pogrebinsky, Gheorghe Doros, Heather Landau
Journal: Blood Cancer Journal (2022)

Abstract Effective systemic therapies suppress toxic light chain production leading to an increased proportion of patients with light chain (AL) amyloidosis who survive longer albeit with end-stage renal disease. There is a critical need to identify patients in this population who benefit from renal transplantation. This multicenter, observational study from five countries includes 237 patients with AL amyloidosis who underwent renal transplantation between 1987 and 2020. With a median follow-up of 8.5 years, the median overall survival from renal transplantation was 8.6 years and was significantly longer in patients with complete and very good partial hematologic responses (CR + VGPR) compared to less than VGPR (9 versus 6.8 years; HR: 1.5, P = 0.04 [95% CI: 1–2.1]) at renal transplantation. Median graft survival was 7.8 years and was better in the CR + VGPR group (8.3 vs 5.7 years, HR: 1.4, P = 0.05 [95% CI: 1–2]). The frequency and time to amyloid recurrence in the graft was also lower (16% vs 37%, p = 0.01) and longer (median time not achieved vs 10 years, p = 0.001) in the CR + VGPR group. Comparing CR vs. VGPR there was no difference in overall or graft survival. Although 69 patients (29%) experienced hematologic relapse, treatment effectively prevented graft loss in the majority (87%). Renal transplantation in selected AL amyloidosis patients is associated with extended overall and renal graft survival. Patients with hematologic CR or VGPR have the most favorable outcomes, and these patients should be considered for renal transplantation.
Studies in the Psychology of Sex. The Evolution of Modesty, the Phenomena of Sexual Periodicity, Auto-Erotism
Journal: JAMA (1900)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Physician-Patient Communication
Authors: Wendy Levinson
Journal: JAMA (1994)

What factors put physicians at risk for being sued? This is a vital question to practicing physicians since being named in a malpractice suit or, worse yet, going to court is an emotionally distressing event. A suit can lead to personal isolation, humiliation, depression, and even physical illness for physicians.<sup>1,2</sup>Understanding malpractice risk factors is also important to malpractice insurance companies, hospitals, and health care systems that seek to provide high-quality care while minimizing their liability and financial risk. See also pp 1583 and 1588. This issue of<i>JAMA</i>contains two articles that explore the relationship between physicians' malpractice claims history and two potential risk factors: quality of medical care and interpersonal communication skills. The study by Entman et al<sup>3</sup>examined the relationship between malpractice claims history of Florida obstetricians and the quality of the clinical care they provided to patients 5 to 10 years after the claims.
Rapid detection of SARS-CoV-2 RNA in saliva via Cas13
Authors: Sita S. Chandrasekaran, Shreeya Agrawal, Alison Fanton, Aditya R. Jangid, Bérénice Charrez, Arturo M. Escajeda, Sungmin Son, Roger Mcintosh, Huyen Tran, Abdul Bhuiya, María Díaz de León Derby, Neil A. Switz, Maxim Armstrong, Andrew R. Harris, Noam Prywes, Maria Lukarska, Scott B. Biering, Dylan C. J. Smock, Amanda Mok, Gavin J. Knott, Qi Dang, Erik Van Dis, Eli Dugan, Shin Kim, Tina Y. Liu, Jennifer R. Hamilton, Enrique Lin-Shiao, Elizabeth C. Stahl, Connor A. Tsuchida, Petros Giannikopoulos, Matthew McElroy, Shana McDevitt, Arielle Zur, Iman Sylvain, Alison Ciling, Madeleine Zhu, Clara Williams, Alisha Baldwin, Erica A. Moehle, Katherine Kogut, Brenda Eskenazi, Eva Harris, Sarah A. Stanley, Liana F. Lareau, Ming X. Tan, Daniel A. Fletcher, Jennifer A. Doudna, David F. Savage, Patrick D. Hsu
Journal: Nature Biomedical Engineering (2022)